Rössler T, Marschalek R
Institute of Pharmaceutical Biology/DCAL, Goethe-University of Frankfurt, Biocenter, Frankfurt/Main, Germany.
Pharmazie. 2013 Jul;68(7):601-7. doi: 10.1055/s-0033-1343653.
The biological process of differentiation - from a fertilized egg to a human being - is a consecutive mechanism that leads to the establishment of tissue-specific gene expression, but also to a coordinated shut-down of all those genes that are not necessary for a given cell type. This process is accompanied by posttranslational modifications of the chromatin (DNA methylation and covalent histone modifications), also termed the "epigenetic layer". All epigenetic processes are mediated by protein complexes that either mediate specific DNA methylation patterns, or modify nucleosomal proteins in a covalent fashion (acetylation, methylation, phosphorylation and ubiquitinylation). One important player involved in epigenetics is the MLL protein which represents a histone H3 methyltransferase. The MLL gene gained much attention because of its frequent genetic rearrangements, thereby creating oncogenic MLL fusion genes that cause acute leukemia in pediatric and adult patients. This article is summarizing certain functional aspects about MLL, but is mainly emphasizing on an alternative splice event within the PHD domain. This changes the biological properties of the MLL protein, thereby influencing its ability of being either a transcriptional activator or repressor.
从受精卵发育为人类的分化生物学过程是一种连续机制,它不仅导致组织特异性基因表达的确立,还导致所有对特定细胞类型不必要的基因的协同关闭。这个过程伴随着染色质的翻译后修饰(DNA甲基化和组蛋白共价修饰),也被称为“表观遗传层”。所有表观遗传过程均由蛋白质复合物介导,这些复合物要么介导特定的DNA甲基化模式,要么以共价方式修饰核小体蛋白(乙酰化、甲基化、磷酸化和泛素化)。参与表观遗传学的一个重要因子是MLL蛋白,它是一种组蛋白H3甲基转移酶。MLL基因因其频繁的基因重排而备受关注,从而产生致癌的MLL融合基因,导致儿童和成年患者患急性白血病。本文总结了MLL的某些功能方面,但主要强调了PHD结构域内的一个可变剪接事件。这改变了MLL蛋白的生物学特性,从而影响其作为转录激活剂或抑制剂的能力。